Standardization of neurophysiology signal data into the DICOM® standard.

A standard format for neurophysiology data is urgently needed to improve clinical care and promote research data exchange. Previous neurophysiology format standardization projects have provided valuable insights into how to accomplish the project. In medical imaging, the Digital Imaging and Communication in Medicine (DICOM) standard is widely adopted. DICOM offers a unique environment to accomplish neurophysiology format standardization because neurophysiology data can be easily integrated with existing DICOM-supported elements such as video, ECG, and images and also because it provides easy integration into hospital Picture Archiving and Communication Systems (PACS) long-term storage systems. Through the support of the International Federation of Clinical Neurophysiology (IFCN) and partners in industry, DICOM Working Group 32 (WG-32) has created an initial set of standards for routine electroencephalography (EEG), polysomnography (PSG), electromyography (EMG), and electrooculography (EOG). Longer and more complex neurophysiology data types such as high-definition EEG, long-term monitoring EEG, intracranial EEG, magnetoencephalography, advanced EMG, and evoked potentials will be added later. In order to provide for efficient data compression, a DICOM neurophysiology codec design competition will be held by the IFCN and this is currently being planned. We look forward to a future when a common DICOM neurophysiology data format makes data sharing and storage much simpler and more efficient.

Association of Periodic and Rhythmic Electroencephalographic Patterns With Seizures in Critically Ill Patients.

IMPORTANCE: Periodic and rhythmic electroencephalographic patterns have been associated with risk of seizures in critically ill patients. However, specific features that confer higher seizure risk remain unclear. OBJECTIVE: To analyze the association of distinct characteristics of periodic and rhythmic patterns with seizures. DESIGN, SETTING, AND PARTICIPANTS: We reviewed electroencephalographic recordings from 4772 critically ill adults in 3 academic medical centers from February 2013 to September 2015 and performed a multivariate analysis to determine features associated with seizures. INTERVENTIONS: Continuous electroencephalography. MAIN OUTCOMES AND MEASURES: Association of periodic and rhythmic patterns and specific characteristics, such as pattern frequency (hertz), Plus modifier, prevalence, and stimulation-induced patterns, and the risk for seizures. RESULTS: Of the 4772 patients included in our study, 2868 were men and 1904 were women. Lateralized periodic discharges (LPDs) had the highest association with seizures regardless of frequency and the association was greater when the Plus modifier was present (58%; odds ratio [OR], 2.00, P < .001). Generalized periodic discharges (GPDs) and lateralized rhythmic delta activity (LRDA) were associated with seizures in a frequency-dependent manner (1.5-2 Hz: GPDs, 24%,OR, 2.31, P = .02; LRDA, 24%, OR, 1.79, P = .05; ≥ 2 Hz: GPDs, 32%, OR, 3.30, P < .001; LRDA, 40%, OR, 3.98, P < .001) as was the association with Plus (GPDs, 28%, OR, 3.57, P < .001; LRDA, 40%, P < .001). There was no difference in seizure incidence in patients with generalized rhythmic delta activity compared with no periodic or rhythmic pattern (13%, OR, 1.18, P = .26). Higher prevalence of LPDs and GPDs also conferred increased seizure risk (37% frequent vs 45% abundant/continuous, OR, 1.64, P = .03 for difference; 8% rare/occasional vs 15% frequent, OR, 2.71, P = .03, vs 23% abundant/continuous, OR, 1.95, P = .04). Patterns associated with stimulation did not show an additional risk for seizures from the underlying pattern risk (P > .10). CONCLUSIONS AND RELEVANCE: In this study, LPDs, LRDA, and GPDs were associated with seizures while generalized rhythmic delta activity was not. Lateralized periodic discharges were associated with seizures at all frequencies with and without Plus modifier, but LRDA and GPDs were associated with seizures when the frequency was 1.5 Hz or faster or when associated with a Plus modifier. Increased pattern prevalence was associated with increased risk for seizures in LPDs and GPDs. Stimulus-induced patterns were not associated with such risk. These findings highlight the importance of detailed electroencephalographic interpretation using standardized nomenclature for seizure risk stratification and clinical decision making.

Reviewing the development, evidence base, and application of the revised dengue case classification.

With the example of dengue, an evidence-based approach to prospectively develop a case classification is described, gathering evidence for identifying strength and weaknesses of the existing model, collecting new data describing the disease as it occurs globally, further developing a new model that can be applied in practice and field testing the newly developed model in comparison to the previous model. For each step in this process, the highest available level of evidence has been applied. This process has been initiated by the World Health Organization's (WHO) Special Programme for Research and Training in Tropical Diseases (TDR) and WHO's Department for Control of Neglected Tropical Diseases (NTD), developing the following for dengue. Since the early 1970s, dengue has been classified into dengue fever, dengue haemorrhagic fever grades I and II and dengue shock syndrome grades III and IV (DF/DHF/DSS). However, in recent years, a growing number of dengue clinicians have questioned the shortcomings of this scheme. The issues have revolved around the complexity of confirming DHF in clinical practice, misclassifying severe cases as DF, and the emphasis on haemorrhage rather than plasma leakage as the underlying problem in most severe dengue cases. Step 1: A systematic literature review highlighted the shortcomings of the DF/DHF/DSS scheme: (1) difficulties in applying the criteria for DHF/DSS; (2) the tourniquet test has a low sensitivity for distinguishing between DHF and DF; and (3) most DHF criteria had a large variability in frequency of occurrence. Step 2: An analysis of regional and national dengue guidelines and their application in the clinical practice showed a need to re-evaluate and standardize guidelines as the actual ones showed a large variation of definitions, an inconsistent application by medical staff, and a lack of diagnostic facilities necessary for the DHF diagnosis in frontline services. Step 3: A prospective cohort study in seven countries, confirmed the difficulties in applying the DF/DHF/DSS criteria even in tertiary care hospitals, that DF/DHF/DSS do not represent levels of disease severity and that a clear distinction between severe dengue (defined by plasma leakage and/or severe haemorrhage, and/or organ failure) and (non-severe) dengue can be made using highly sensitive and specific criteria. In contrast, the sub-grouping of (non-severe) dengue into two further severity levels was only possible with criteria that gave approximately 70% sensitivity and specificity. Step 4: Three regional expert consensus groups in the Americas and Asia concluded that 'dengue is one disease entity with different clinical presentations and often with unpredictable clinical evolution and outcome' and that, revising the results of Step 3, DF/DHF/DSS is not related to disease severity. Step 5: In a global expert consensus meeting at WHO in Geneva/Switzerland the evidence collected in Steps 1-4 was reviewed and a revised scheme was developed and accepted, distinguishing: dengue with or without warning signs and severe dengue; the further field testing and acquisition of further prospective evidence of the revised scheme was recommended. Step 6: In 18 countries, the usefulness and applicability of the revised classification compared to the DF/DHF/DSS scheme were tested showing clear results in favour of the revised classification. Step 7: Studies are under way on the predictive value of warning signs for severe dengue and on criteria for the clinical diagnosis of dengue which will complete the evidence foundation of the revised classification. The analysis has shown that the revised dengue case classification is better able to standardize clinical management, raise awareness about unnecessary interventions, match patient categories with specific treatment instructions, and make the key messages of patient management understandable for all health care staff dealing with dengue patients. Furthermore, the evidence-based approach to develop prospectively the dengue case classification could be a model approach for other disease classifications.

Effects of thoracic epidural analgesia on glucose homeostasis after cardiac surgery in patients with and without diabetes mellitus.

BACKGROUND AND OBJECTIVE: Even moderate hyperglycaemia increases mortality/morbidity after coronary artery bypass grafting, stroke and myocardial infarction. The goal of this prospective study was to determine if using thoracic epidural analgesia from start of surgery until the end of the third postoperative day would blunt postoperative hyperglycaemia. METHODS: Forty-four patients had diabetes mellitus, 60 did not; half of each group had an epidural with continuous local anaesthetics. All patients received continuous insulin infusions during the initial 24 h period beginning with surgery. Blood glucose was measured four times daily (fasting or 2-3 h post-prandial) until end of the third postoperative day. RESULTS: For patients without diabetes, the epidural group had lower mean blood glucose and insulin requirements (P < 0.02) than controls during the initial 24 h period beginning with surgery. For patients with diabetes mellitus, thoracic epidural analgesia reduced mean blood glucose (P = 0.017) with unchanged insulin requirements. Epidural did not diminish the increase (vs. preoperative) in fasting blood glucose on the third postoperative day (32% vs. 22%, P < 0.001) for non-diabetics. Epidural analgesia was not able to attenuate hyperglycaemia during the first 3 postoperative days. CONCLUSIONS: Epidural analgesia improved glucose homeostasis minimally during the initial 24 postoperative hours but did not attenuate hyperglycaemia during the subsequent 3 postoperative days.

Retrograde crystalloid cardioplegia preserves left ventricular systolic function better than antegrade cardioplegia in patients with occluded coronary arteries.

OBJECTIVE: To investigate retrograde and antegrade crystalloid cardioplegia in terms of cardiac cooling and postoperative cardiac function. DESIGN: Prospective, randomized, and blinded. SETTING: University hospital. PARTICIPANTS: Twenty male patients with triple-vessel disease and proximal occlusion of the circumflex or the left anterior descending coronary artery. INTERVENTIONS: Left ventricular ejection fraction at rest and during exercise was evaluated by nuclear ventriculography the day before and 3 months after surgery. After induction of anesthesia and hourly for the first 5 postoperative hours, hemodynamic, echocardiographic, and electrocardiographic data were acquired. Myocardial temperature was measured with needle thermistors in 3 myocardial regions. MEASUREMENTS AND MAIN RESULTS: Demographic and temperature data were analyzed by t-test. Hemodynamic and echocardiographic data were analyzed by analysis of variance. The groups were similar in baseline characteristics. Retrograde cardioplegia cooled the region distal to an occlusion better than antegrade cardioplegia (9.6 degrees C +/- 4.8 degrees C v 21.8 degrees C +/- 5.9 degrees C; p < 0.01). Hemodynamic, echocardiographic, and electrocardiographic data did not differ between the groups. Three months after surgery, the retrograde cardioplegia group showed a higher left ventricular ejection fraction at rest (58% +/- 10% v 47% +/- 10%; p < 0.02) and during exercise (58% +/- 13% v 47% +/- 10%; p < 0.05) compared with the antegrade cardioplegia group. CONCLUSIONS: Retrograde cardioplegia provides more homogenous myocardial cooling than antegrade cardioplegia in hearts with coronary artery occlusions. The use of retrograde cardioplegia seems to benefit long-term left ventricular function.

Clinical estimation of left and right ventricular volume with open chest compared with transesophageal echocardiography and fast-response thermodilution.

OBJECTIVE: A clinical measure--inspection of the relation of the heart (acute margin) to the diaphragm--has shown a strong positive correlation to transesophageal echocardiographic (TEE) determination of left ventricular end-diastolic area (LVEDA) during weaning from cardiopulmonary bypass (CPB). The present study examines the correlation between right ventricular end-diastolic volumes (RVEDV) before and after CPB when using the same clinical measure of left ventricular dimension. DESIGN: Prospective study. SETTING: Operating room, university hospital. PARTICIPANTS: Patients scheduled for elective coronary artery bypass grafting. INTERVENTIONS: After induction of anesthesia and endotracheal intubation, a transesophageal echo-probe was inserted. A pulmonary artery right ventricular ejection fraction/volumetric TD catheter was placed in the pulmonary artery. MEASUREMENTS AND MAIN RESULTS: Before going on CPB, a mark was made with cautery at the line of contact between the acute margin and the diaphragm. After CPB, the patients were transfused to the same level. At these two times, TEE recordings of the LVEDA and hemodynamic measurements including calculations of RVEDV were obtained. The LVEDA before and after CPB showed a positive correlation, r = 0.81, p < 0.001. The RVEDV after CPB showed a weak correlation, r = 0.54, p < 0.05, to RVEDV before CPB. There were no significant changes in right ventricular (RV) wall tension calculated as right atrial pressure x RVEDV and pulmonary artery systolic pressure x right ventricular end-systolic volume products. The only significant change regarding hemodynamic parameters was a decrease in mean arterial pressure. CONCLUSIONS: It is concluded that there is only a weak correlation regarding RVEDV before and after CPB when the patient is transfused to the line of contact, whereas this clinical measure correlates well with LVEDA.

Effects of low-dose adenosine on myocardial performance after coronary artery bypass surgery.

The effect of a non-hypotensive dose of adenosine infusion on myocardial performance after coronary artery bypass surgery was examined. Upon arrival at the intensive care unit, 16 patients (14 males, 2 females; mean age 64.5, range 46-71) were randomized to a blinded infusion of either low-dose adenosine (n = 8) or placebo (n = 8). The infusion continued at a rate corresponding to 30 micrograms.kg-1.min-1 of adenosine into the right ventricle over 4 h. Data were collected from the arterial line, thermodilution pulmonary artery catheter, transoesophageal echocardiogram (TEE), and 12-lead ECG on six occasions: before infusion, hourly during the infusion, and 1 h after terminating the infusion. Mean arterial blood pressure did not differ between the adenosine and placebo groups at any measurement point. Heart rate increased by approximately 15% during the first hour of adenosine infusion. Cardiac index increased by approximately 50% during infusion of adenosine and cardiac index remained higher while systemic vascular resistance remained lower in the adenosine-treated group during infusion. The E/A ratio (ratio between peak left ventricular inflow blood velocities during early filling and atrial contraction) was significantly higher in the adenosine-treated group after treatment for 1 h while the area injection fraction did not differ between groups at any time. The number of patients with ischaemic events as judged from ECG and from left ventricular regional wall motion abnormalities (RWMA) as visualized by TEE did not differ between groups (ECG: one patient in the adenosine group and one patient in the placebo group-RWMA: four patients in the adenosine group versus three in the placebo group).(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial ischaemia as judged from transoesophageal echocardiography and ECG in the early phase after coronary artery bypass surgery.

The incidence of myocardial ischaemia, as diagnosed by transoesophageal echocardiography (TEE) versus ECG, and the relationship between ischaemic events and haemodynamic parameters were studied in 30 patients in the early phase after coronary artery bypass grafting. Information comprising invasive haemodynamics, TEE measurements, and 12-lead ECG was obtained on arrival of the patient in the intensive care unit (ICU), and then hourly in the ICU for 5 h. In the ICU, TEE signs of ischaemia were found in 14 patients and ECG signs of ischaemia in six patients. The ischaemic events were not related to levels of blood pressure or heart rate. Three patients showed signs of myocardial infarction postoperatively. All three of these patients showed both TEE and ECG signs of ischaemia in the ICU. It was concluded that TEE reveals more ischaemic events than ECG in the early postoperative period and that these ischaemic events do not correlate with the haemodynamic indices.

T cell responses to fractionated Mycobacterium leprae antigens in leprosy. The lepromatous nonresponder defect can be overcome in vitro by stimulation with fractionated M. leprae components.

Protective immunity against Mycobacterium leprae is dependent on M. leprae-reactive T lymphocytes. M. lepare-directed T cell reactivity is high in the localized tuberculoid form of leprosy but specifically absent in the disseminated lepromatous type of the disease. Two important questions that are relevant for the understanding of the immune response in leprosy as well as for the design of rational immunoprophylaxis and -therapy strategies are: (a) what are the antigens that trigger T cell responses in tuberculoid patients and thus protect these individuals from developing lepromatous leprosy and (b) is it possible to restore T cell responsiveness to M. leprae in lepromatous patients by rechallenging the immune system with selected antigens that will trigger help but not suppression? We have addressed these question by directly probing the peripheral T cell repertoire of 10 tuberculoid and 18 lepromatous patients with large numbers of different M. leprae and BCG antigenic components that had been separated on the basis of their relative molecular mass (Mr) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroblotted onto nitrocellulose. This technique allows the identification of T cell-stimulating antigens independent of the expression of B cell epitopes by these antigens. So far T cell epitopes have only been mapped on M. leprae proteins that had previously been defined by antibodies. Our results show that: (a) tuberculoid patients' T cells responded preferentially to M. leprae and BCG antigens in the lower (i.e. less than 70 kDa) Mr range with a peak in the 10-25 kDa range; (b) 6 out of 18 lepromatous patients that did not respond to whole M. leprae responded strongly to isolated M. leprae components; antigens in the lower Mr. range were recognized by five out of these six patients and thus commonly seen by both tuberculoid and lepromatous patients' T cells; however, antigens in the higher Mr range, in particular greater than 150 kDa, were only recognized by lepromatous patients' T lymphocytes; (c) furthermore, the T and B cell repertoires in leprosy patients are skewed towards different antigenic fractions.

Cellular, humoral, and gamma interferon responses to Mycobacterium leprae and BCG antigens in healthy individuals exposed to leprosy.

Protective immunity against mycobacteria is dependent on antigen-specific T cells. The antibodies induced upon immunization with mycobacteria have no apparent role in host protection. Serological techniques have detected some antigens that are also recognized by human T cells but may fail to recognize others. Potentially, there may be differences in the epitopes seen by the T and B cell anti-mycobacterial antigen repertoires. We have screened the different components of sonicated BCG or Mycobacterium leprae that were separated according to their molecular weight (MW) by SDS-PAGE and then electroblotted on nitrocellulose paper. The blots were cut into squares and tested directly in a T cell proliferation assay. Our results indicate that peripheral T cells of healthy leprosy patient contacts respond preferentially to the lower MW (less than 70,000) and not the higher MW fractions of M. leprae and BCG, in contrast to the humoral response of these same individuals. The most important fractions in inducing a lymphoproliferative response were in the regions of 11-16 kDa of BCG and M. leprae and to the 22-26 kDa region of M. leprae. These fractions appeared to represent molecular weight regions that were in some instances clearly distinct from previously defined antigens. It was further shown that lymphoproliferation in response to mycobacterial fractions correlated with the production of gamma interferon, a lymphokine required for macrophage activation and elimination of mycobacteria. These studies allow the direct assessment of antigens involved in protective T cell-mediated immunity, and should be helpful in selecting relevant antigens for skin testing and immunization.

Analysis of the antigenic profile of Mycobacterium leprae: cross-reactive and unique specificities of human and rabbit antibodies.

Thirty-two mycobacterial components were detected by antibodies contained in leprosy patients' sera across the clinical spectrum and rabbit anti-M. leprae hyperimmune sera by western blot analysis of armadillo-derived M. leprae antigen preparations. Sera of borderline tuberculoid patients were found to contain antibodies recognizing 18 M. leprae components. While the reactivity of the sera on the lepromatous pole seemed to be distributed over the entire molecular weight range, most of the reactivity in the borderline tuberculoid patients was directed at higher molecular weight components (greater than 70,000). Identification of a series of previously unrecognized M. leprae components offers new possibilities in regard to the potential use of these antigens as targets for immunodiagnosis. Antibodies contained in the rabbit anti-M. leprae sera reacted with 19 M. leprae components. Antigens migrating at 64,000, 38,000, and 22,000 were detected by the rabbit sera only. Evidence of extensive cross-reactivity between M. leprae and BCG organisms emphasizes the need to use well-characterized antibody probes to determine the specificity of select mycobacterial antigens. The potential usefulness of rabbit monospecific hyperimmune sera to select M. leprae fractions in immunodiagnosis, in immune regulation studies, or as a tool to screen for mycobacterial products in lambda gt11 phage lysates of E. coli is discussed. Select M. leprae components were partially purified and their recovery assessed through SDS-PAGE analysis of Coomassie blue-stained gels.

Dirofilaria immitis: identification and characterization of circulating parasite antigens.

A method for the identification of circulating parasite antigens in filarial nematode infections was developed using canine infections with Dirofilaria immitis as a model. Filarial antigens ranging in molecular weight from 211 to 13 kDa were extracted from the sera of microfilaremic dogs by a solid phase immunobinding procedure and identified by immunostaining of Western blots. A major antigen of 104 kDa was selected for further characterization. The 104 kDa circulating antigen showed antigenic and biochemical identity with 104 kDa peptides found in extracts of adult male and microfilarial stages of the parasite. The 104 kDa peptide was antigenically stable under a variety of storage conditions. Its potential as a diagnostic target is discussed.

Antigenic peptides on the surface of Dirofilaria immitis microfilariae.

Various methods of radioiodination were employed to identify peptides on the surface of Dirofilaria immitis microfilariae. Optimum surface radiolabelling occurred with the lactoperoxidase-catalyzed reaction. Two major peptides of 16 and 14 kDa were labelled by this method. These peptides were soluble in Nonidet P-40, were not glycosylated, and showed no signs of disulfide linkages. These peptides were immunoprecipitated by sera from D. immitis-infected dogs, but not by sera from uninfected dogs or sera from dogs with potentially cross-reactive nematode infections. Analysis of the 14 and 16 kDa peptides by two-dimensional gel electrophoresis revealed that the 16 kDa peptide was a single unit with a pI of 5.25 whereas the 14 kDa band was composed of three individual peptides with pI values ranging from 5.6 to 6.1. Iodination by chloramine T resulted in the same panel of labelled peptides but suffered from poor efficiency of 125I incorporation. The viability of microfilariae labelled by the standard Bolton-Hunter method decreased by 50% following the reaction which resulted in the labelling of a variety of internal components.